Fetal Transplant Takes Root in Huntington's Patient

Findings Could Pave the Way to New Therapies

November 30, 2000 -- Belmont, MA -- Human fetal neurons sown into the brain of a 54-year-old man with Huntington's disease, a hereditary and fatal neurodegenerative disease, survived 18 months after transplantation. Remarkably, the cells, taken from nine-week old fetuses, appeared to be untouched by the cellular destruction raging around them, McLean Hospital researchers working with scientists from the University of South Florida and other institutions report in the December 5 Proceedings of the National Academy of Science.

"This is the first demonstration that these cells can survive. And they are not affected by the genetic disease of the surrounding cells," says Francesca Cicchetti, PhD, research fellow at McLean's Neuroregeneration Laboratory. She and Thomas Freeman of the University of South Florida are lead authors of the paper.

Previous attempts to replenish sick or lost brain cells with fetal neurons have been aimed at people with Parkinson's disease, another neurodegenerative disease. This is the first time that transplanted fetal neurons have been shown to actually take root in a patient with Huntington's disease.

"Everybody said ten years ago that this was outlandish—you can’t transplant cells into a toxic brain—those new cells will die," says Ole Isacson, MD, director of McLean's Neuroregeneration Labs and a coauthor of the study.

Although it is unclear whether the transplanted fetal cells carried out functions in the patient's brain, the fact that they were able to thrive a year and a half after transplantation is good news not just for the fetal cell transplantation community but also for those seeking to use stem cells—protean cells with the ability to become any cell type—to replace the damaged or missing neurons of people with Huntington's and other neurodegenerative diseases. "Stem cells need to be coaxed into becoming fetal neurons," says Isacson. "If fetal cells work in Parkinson's and Huntington's disease, then all the claims made for stem cells will be more realistic," Isacson says.

Huntington's disease, which affects 30,000 Americans, is due to a genetic defect that results in the clumping of a deadly protein in the striatum, an area of the brain involved in controlling motion. Although the genetic defect was discovered in 1983, there are no treatments for the disease.

To explore the therapeutic possibility of transplantation, Freeman and colleagues at the University of South Florida introduced whole fetal striata into the brains of seven Huntington's disease patients—ten fetal striata per patient. When one of the subjects, a 54 year-old man died suddenly of a heart attack a year and a half later, Freeman called upon Cicchetti, Isacson and their colleagues at McLean to analyze the man's brain.

Upon inspection, the researchers found that most of the fetal implants had taken root in the man's striatum. What is more, they lacked the poisonous protein clumps found in the surrounding sick cells. Nor did the newcomer neurons exhibit signs that they had been immunologically rejected by their host.

It is not clear whether the new cells have formed connections in part because it is hard to distinguish which fibers are from the transplanted striatal cells and which from host cells, say Cicchetti and Isacson.

Nor is it clear that the transplants improved the patient's functioning. Although the man reported some change, it was not found to be significant when measured in clinical tests. "Whether more transplanted tissue would be better we don’t know," says Cicchetti. The transplanted fetal striatal cells accounted for only 5 to 10 percent of the total volume of the man's striatum.

Intriguingly, Marc Peschanski and colleagues report in this week’s Lancet that, using brain imaging methods, they have found significant functional changes in the brains of Huntington's disease patients who received transplanted human fetal cells.

In earlier studies, Isacson and his colleagues found that transplanting fetal cells restored function to animals with Huntington's disease-like damage and symptoms. "We certainly can make the animals improve," Isacson says. "The question is what kinds of development we need to have success in patients."

"These new technologies are under intense development. We need to improve all aspects of this work to make it as effective as has been shown in animals," he says.